MOLECULAR PHYLOGENY OF ANNEXINS AND IDENTIFICATION OF A PRIMITIVE HOMOLOG IN GIARDIA-LAMBLIA

The homologous repeats of annexin tetrads are believed to have origina ted by successive duplication and fusion from a putative monomeric pre cursor, but neither the nature of their ancestor nor the events leadin g to the formation of different subfamilies have been elucidated. We h ave performed molecular phylogenetic analysis of aligned annexin nucle otide and amino acid sequences to characterize subfamily branching, to delineate the temporal order of appearance of individual repeat units , and to gain insight into the origin and nature of the primordial uni t. All extant annexins appear to have a common tetrad precursor that m ay have originated from a progenitor unit resembling repeat 3, followe d by the generation of repeats 4, 1, and 2 from a more evolved progeni tor with subsequent fusion. Repeat sequences of the earliest human ann exins VII and XIII were used to identify alpha-giardin genes as primit ive homologues from the unicellular protozoan Giardia lamblia, which d iverged from eukaryote lineage 1-1.5 billion yr ago. The significant h omology between alpha-giardins and annexins suggested that the cell me mbrane adhesive role of these proteins may be a common, fundamental pr operty of the annexin C-terminal core region. Purported annexin VII of Dictyostelium discoideum was reclassified as new annexin XIV, three C aenorhabditis elegans genes were assigned to new subfamilies XV, XVI, and XVII, and plant annexin XVIII from Medicago saliva was among the e arliest diverging subfamilies. Annexins I and II were found to be clos ely related, but analysis of protein mutation rates confirmed that the former is evolving up to three times more rapidly. The inclusion of e arly phyla in annexin taxonomy provides a useful basis for assessing t he structural and functional changes associated with annexin evolution .